15-73927771-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005576.4(LOXL1):​c.988C>T​(p.Pro330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000779 in 1,283,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62
Variant links:
Genes affected
LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]
LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25000915).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LOXL1NM_005576.4 linkuse as main transcriptc.988C>T p.Pro330Ser missense_variant 1/7 ENST00000261921.8 NP_005567.2
LOXL1-AS1NR_040069.1 linkuse as main transcriptn.184+294G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LOXL1ENST00000261921.8 linkuse as main transcriptc.988C>T p.Pro330Ser missense_variant 1/71 NM_005576.4 ENSP00000261921 P1
LOXL1-AS1ENST00000685373.1 linkuse as main transcriptn.198+6G>A splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.79e-7
AC:
1
AN:
1283054
Hom.:
0
Cov.:
33
AF XY:
0.00000159
AC XY:
1
AN XY:
630778
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000491
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 20, 2021The c.988C>T (p.P330S) alteration is located in exon 1 (coding exon 1) of the LOXL1 gene. This alteration results from a C to T substitution at nucleotide position 988, causing the proline (P) at amino acid position 330 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
0.77
N
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.025
Sift
Benign
0.18
T
Sift4G
Benign
0.068
T
Polyphen
0.90
P
Vest4
0.24
MutPred
0.27
Gain of relative solvent accessibility (P = 0.0023);
MVP
0.48
ClinPred
0.95
D
GERP RS
3.0
Varity_R
0.13
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1308963221; hg19: chr15-74220112; API